SUMMARY Over half of newborns develop jaundice, a condition caused by high levels of bilirubin in the blood. Bilirubin is neurotoxic and when it accumulates in the brain it can cause seizures and death, as well as long-term consequences such as cerebral palsy and hearing impairment. It has been known for decades that visible light can be used to treat neonatal jaundice through light-catalyzed conversion of bilirubin to nontoxic products. However, conventional phototherapy is a slow process because light penetration is limited to a small layer at the surface of the skin. Because of the high risk of brain damage, phototherapy is inadequate for treating severe cases of jaundice. Instead, these newborns are treated using exchange transfusion, a process that involves replacement of the neonate's blood with donor blood. Exchange transfusion can have serious complications, including uncontrolled bleeding and infection, and is associated with significant morbidity in 10% of cases. Severe jaundice affects about 30,000 newborns per year in the US and over a million newborns worldwide. Thus, there is a significant need for new technologies that enable rapid and safe treatment of jaundice. The proposed work focuses on development of a microfluidic photoreactor for extracorporeal blood treatment to reduce bilirubin levels. The key advantage of the device is that the microfluidic length scale overcomes challenges associated with light attenuation, allowing illumination of the entire blood volume passing through the device. Preliminary studies show that the device enables bilirubin levels to be reduced as quickly as exchange transfusion, while also maintaining a small device volume and low blood flow rate for improved safety. To further improve safety, the blood contacting surfaces in the extracorporeal circuit will be coated to impart biocompatibility and anticoagulant function using a polyethylene oxide (PEO) brush layer, with heparin tethered in a highly-active end-on fashion at the PEO chain ends. Preliminary studies demonstrate protein-repellent characteristics and strong anticoagulant function of the proposed coating, highlighting the potential for operation of the extracorporeal circuit without systemic anticoagulants. This is significant because neonates are particularly susceptible to complications associated with the use of systemic anticoagulants, such as intracranial hemorrhage. Based on our promising preliminary results, the proposed research examines the central hypothesis that bilirubin can be rapidly and safely removed without systemic anticoagulation using a heparin-coated microfluidic photoreactor. This hypothesis will be tested by first identifying design features for safe and effective bilirubin conversion in the photoreactor, as well as criteria for surface coatings that lead to effective anticoagulant function. The resulting data will be used to develop an integrated photoreactor system, which will then be tested for safety and efficacy using a Gunn rat model. This work represents an important step toward clinical translation of the photoreactor technology, and also paves the way for application of the anticoagulant coating to other medical device surfaces (e.g., catheters, membrane oxygenators).